Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat.
The effects of the pineal hormone, melatonin, and of pinealectomy on the incidence of mammary adenocarcinoma in Sprague-Dawley rats treated with 7,12-dimethylbenz(alpha)-anthracene (DMBA) were investigated. Melatonin (2.5 mg/kg), begun on the same day as DMBA (5 mg) treatment and given daily in the afternoon for 90 days, significantly reduced the incidence of mammary tumors from 79% (control) to 20% (treated) (p less than 0.002). Rats pinealectomized at 20 days of age and treated with 7 mg of DMBA at 50 days of age had a higher incidence of tumors (88%) compared to control animals (22%). Fifteen mg of DMBA, which resulted in a higher incidence of tumors, reduced the difference between pinealectomized and control animals. Melatonin only partially reversed the effects of pinealectomy, reducing the incidence from 87% (pinealectomy alone) to 63% (pinealectomy plus melatonin); however, the tumor incidence was still lower (27%) in nonpinealectomized, melatonin-treated animals. Assessment of plasma prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, and cortisol in DMBA-treated tumor-free and tumor-bearing animals revealed a significantly lower plasma prolactin concentration [27 +/- 5 (S.E.) ng/ml] in melatonin-treated animals as compared to vehicle-treated animals [65 +/- 8 ng/ml]. The concentration of plasma prolactin was less in melatonin-treated, pinealectomized rats (55 +/- 10 ng/ml) as compared to vehicle-treated, pinealectomized animals (101 +/- 13 ng/ml). Other hormones were not affected by melatonin treatment. These data support the hypothesis that melatonin inhibits the development of DMBA-induced mammary tumors in the rat while removal of the pineal gland stimulates development of such tumors. Additionally, these experiments provide evidence that these effects may be mediated by a suppression of plasma prolactin levels.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D001551:Benz(a)Anthracenes; D002940:Circadian Rhythm; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D008550:Melatonin / Q000494:pharmacology*; D009376:Neoplasms, Hormone-Dependent; D010870:Pineal Gland / Q000502:physiology*; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001551:Benz(a)Anthracenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin; D008550:Melatonin